Interleukin-11 (IL-11) is a cytokine that stimulates proliferation and differentiation of megakaryocytes, which are precursors to platelets. Recombinant human IL-11 is used to stimulate platelet production in patients with thrombocytopenia resulting from myelosuppressive chemotherapy. IL-11 has a short in vivo half-life and must be administered by daily injections. We propose to create modified IL-11 proteins that are equal or superior to natural IL- 11 at stimulating platelet formation in vivo, but which require less frequent dosing, on the order of once per week or once every other week. During Phase I we will identify sites in IL-11 that can be modified without significantly affecting the protein's in vitro bioactivity. During Phase II, we will manufacture sufficient quantities of the modified IL-11 proteins for testing in animal models of thrombocytopenia. The improved characteristics of the novel IL-11 proteins will reduce the amount of IL-11 required per patient, improve patient compliance and quality of life and result in considerable cost savings to patients and healthcare providers. Information gained from these studies will aid in creating long-acting versions of structurally related cytokines and growth factors for use in treating cancer, infectious disease and hematopoeitic disorders. PROPOSED COMMERCIAL APPLICATIONS: Recombinant human IL-11 is used to restore platelet production in patients with thrombocytopenia resulting from chemotherapy. The U.S. market for platelet-stimulating agents is estimated to be in excess of $300 million. The modified IL-11 proteins under development will require much less frequent dosing than existing products, providing significant cost savings to patients and healthcare providers. Additional potential benefits include improved drug efficacy and improved patient quality of life.